136 VITAMINS A AND CAROTENES 



the absence or presence of vitamin A in the diet. Although it has long been 

 realized that precipitating factors in addition to hereditary factors combine 

 in etiology of certain postnatal diseases (diabetes, pernicious anemia), this 

 is the first instance where an antenatal precipitating factor has been 

 demonstrated. 



In view of the specific arrestment of postnatal replacement bone groAvth 

 and the atrophy and keratinizing metaplasia of many epitheliums at all 

 ages resulting from vitamin A deficiency, the consequences of the maternal 

 deficiency upon the development of the fetus are not remarkable. Further 

 experimentation is necessary to correlate congenital defects with degrees 

 and timing of the maternal deficiency and with fetal developmental se- 

 ([uences. Such experimentation would further the study of the role of 

 human maternal deficiencies in the causation of congenital malformations. 



E. SUMMARY 



The morphologic consequences of deficiency and excess of vitamin A 

 place this substance in unique position among the vitamins. It is the only 

 vitamin which, given in amounts in great excess over normal physiologic 

 requirements, produces acceleration of a growth process (skeletal) unrelated 

 to the growth of the organism as a whole. It is necessary for growth and 

 differentiation of epiphyseal cartilage and for the maintenance of differen- 

 tiation of many epithelia but not for their growth. 



Its role in vision has been beautifully and completely elucidated, but 

 otherwise its in vivo chemistry is unknown. 



In spite of the behaviors suggestive of hormone-like properties, there 

 is no evidence that it acts through an endocrine intermediary and there is 

 considerable histologic evidence that it does not. It has been proved in 

 this laboratory that the acceleration of skeletal growth sequences in hyper- 

 vitaminosis A is unaffected in hypophysectomized rats. Similar proof is 

 perhaps necessary for the exclusion of other endocrine glands as inter- 

 mediaries. Impressive evidence that vitamin A acts directly upon com- 

 petent tissues is furnished by experiments of Fell and Mellanby.^^ The 

 cultivation of the ectoderm of chick embryos in media containing exces- 

 sive vitamin A resulted in suppression of the formation of keratinizing 

 epithelia and the substitution of a mucus-secreting ciliated epitheliimi. 

 Explants into a normal medium resulted in differentiation of the basal cells 

 into squamous keratinizing epithelium. 



Results as described make obvious some possibilities of vitamin A ex- 

 perimentation for the anatomist, the embryologist, and, above all, the 



62 H. B. Fell and E. Mellauby, J. Physiol. 119, 470 (1952)]. 



